Sodium Carbonate → (R)-tert-butyl 1-(4-(2-cyano-5-fluorobenzyl)-6-methyl-5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)piperidin-3-ylcarbamate

HRID 240283

反応式

HRID 240283 の反応式
C([O-])([O-])=O.[Na+].[Na+].Br[C:8]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:9]=1[CH2:10][N:11]1[C:16](=[O:17])[C:15]([CH3:18])=[N:14][N:13]=[C:12]1[N:19]1[CH2:24][CH2:23][CH2:22][C@@H:21]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:20]1.[CH3:38][N:39]1C(=O)CCC1>CC(O)C.O.CC([O-])=O.CC([O-])=O.[Pd+2].[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.[K+].[K+].[K+].[K+].[Fe+2]>[C:38]([C:8]1[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:9]=1[CH2:10][N:11]1[C:16](=[O:17])[C:15]([CH3:18])=[N:14][N:13]=[C:12]1[N:19]1[CH2:24][CH2:23][CH2:22][C@@H:21]([NH:25][C:26](=[O:32])[O:27][C:28]([CH3:31])([CH3:30])[CH3:29])[CH2:20]1)#[N:39]

参加物

9

反応物 3

HCID 10340Sodium CarbonateHCID 13387N-methyl-2-pyrrolidone2 回HCID 58328539(R)-tert-butyl 1-(4-(2-bromo-5-fluorobenzyl)-6-methyl-5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)piperidin-3-ylcarbamate

生成物 1

HCID 58328541(R)-tert-butyl 1-(4-(2-cyano-5-fluorobenzyl)-6-methyl-5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)piperidin-3-ylcarbamate

試薬・触媒・溶媒 5

HCID 962Water触媒HCID 3776Isopropanol触媒HCID 167845palladium(II) acetate触媒HCID 9605257Potassium Ferrocyanide触媒HCID 962Water溶媒

実験手順

To a mixture of Na2CO3 (53 mg, 0.50 mmol) and Pd(OAc)2 (3 mg, 0.013 mmol) in NMP (0.5 mL) was added i-PrOH (3 drops) and water (2 drops). The mixture was stirred at RT for 5 min. A solution of (R)-tert-butyl 1-(4-(2-bromo-5-fluorobenzyl)-6-methyl-5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)piperidin-3-ylcarbamate (18, 246 mg, 0.496 mmol) in NMP (1.0 mL) was added. The mixture was heated to 140° C. and then K4[Fe(CN)6].3H2O (209 mg, 0.496 mmol) was added. The mixture was heated at 140° C. for 12 h. After cooling to RT, the mixture was diluted with water (10 mL), and extracted with EtOAc (20 mL×2). The combined extracts were washed with brine, dried over MgSO4, and concentrated to give crude product. This was purified by column chromatography on silica gel, and eluted with 20-35% EtOAc in petroleum ether to provide (R)-tert-butyl 1-(4-(2-cyano-5-fluorobenzyl)-6-methyl-5-oxo-4,5-dihydro-1,2,4-triazin-3-yl)piperidin-3-ylcarbamate (20). MS: m/z, 418 (20%), 443 (100%, M+1), 465 (95%, M+23).

後処理

  1. temperatureThe mixture was heated to 140° C.
  2. addition3H2O (209 mg, 0.496 mmol) was added
  3. temperatureThe mixture was heated at 140° C. for 12 h
  4. temperatureAfter cooling to RT
  5. extractionextracted with EtOAc (20 mL×2)
  6. washThe combined extracts were washed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. customto give crude product
  10. customThis was purified by column chromatography on silica gel
  11. washeluted with 20-35% EtOAc in petroleum ether

出典と根拠

ORDレコード
ord-e9c007889adb434db9ab53c1e29613b5
出典データセット
uspto-grants-2014_02
特許番号
US08648073B2

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